For many years, a variety of animal tissues, as well as some synthetic polymers, have been used to make prosthetic devices for surgical implantation into human beings and other animals. However, because these devices are different on a molecular level from the host organism's own tissue, they usually elicit a wide variety of reactions in the host. The response is manifested by a low-grade, rapid deterioration of the transplant, which in turn, mandates additional surgery.
To improve the longevity of transplanted devices, a number of remedies have been proposed. In the processing of natural tissues, a common stabilization technique involves treatment with tanning agents, such as formaldehyde. Glutaraldehyde, a well known cross-linking agent, has also been used with success in this regard. In fact, a number of studies have shown that heart valves treated with glutaraldehyde can remain functional in situ for many years. However, recent research has indicated that such glutaraldehyde preserved implantations can still elicit significant host reactions, including calcification, fibrin deposition and an anaphylactic response. (For example, see Slanczka, D. J. and Bajpai, P. K., "Immunogenicity of Glutaraldehyde-treated Porcine Heart Valves", IRCS Medical Science: Bio-Technology; Cardiovascular System; Immunology and Allergy; Pathology; Surgery and Transplantation; 6, 421 (1978).)
It has also been theorized that natural prosthetics may be biodegradable, and thus labile even after short placement periods. In vitro enzyme degradation of the tissues prior to implantation has been utilized to minimize this obstacle, but this degradation is not totally effective in mitigating the antigenic response; and moreover, the tissue can lose significant portions of its inherent structural framework, which can cause further mechanical weakening of the entire device.
Although considerable success has been achieved by implanting synthetic devices instead of natural devices, at present, they also present significant difficulties. There is a substantial biological failure rate among these devices due to incompatibility with biological tissues. After removal of the implant, fibrin layering, aneurysm formation, lipid deposition and many clinical malfunctions have been noted.
A further problem, common to many of the synthetic and natural prosthetics alike, is minimal flexibility. Glutaraldehyde-treated natural devices are often cross-linked to such a degree that much of their natural flexibility is lost, and after prolonged periods of implantation, brittleness often becomes even more pronounced. Similarly, synthetic devices generally become increasingly hardened after prolonged implantation.
Therefore, there is a recognized need for an improved treatment of prostheic devices prior to implantation, which will render these devices more durable, yet minimize negative host responses. The present invention fulfills this need.